Original Article
Serum vitamin D levels in primary hypothyroidism
1* 2 3 R Priya , K CVasudha , P Kalra
{1PG Student, 2Profess or, Department of Biochemistry} {3Associate Professor, Department of Endocrinology} M S Ramaiah Medical College, Bangalore, Karnataka, INDIA. Email: [email protected]
Abstract Introduction: Hypothyroidism is a common endocrine disorder with a prevalence rate of 10.95% in India. Primary hypothyroidism is the dysfunction at the level of thyroid gland, leading to decrease secretion or action of thyroid hormones. Vitamin D deficiency/ insufficien cy are very prevalent in general population. In recent years the role of Vitamin D in body was extensively researched. It has been seen that besides having role in bone metabolism, Vitamin D is involved with pathology of various chronic diseases like diabe tes, psoriasis, autoimmune diseases. This study was aimed to see the relationship between primary hypothyroidism and serum Vitamin D deficiency/insufficiency. Method: It was a case control study including 57 newly diagnosed hypothyroid cases of age group 2 0 50 years and 29 age and sex matched controls. Patients were selected based on serum TSH levels according to ATA guidelines. Any other underlying disorder was ruled out after taking proper medical history. Serum levels of 25(OH)D was measured by ELISA. TS H and thyroid hormones were measured by ECLIA. Result: The statistical analysis was done using SPSS version 20.0 software for Windows. The hypothyroid cases showed a median value with an inter quartile range of 14.9(13.4 21.35) for Vitamin D (ng/mL). The m edian value with an inter quartile range for Vitamin D in controls was26.2 (20.45 32.8). Comparing the serum Vitamin D levels between hypothyroid group and controls, a significant p value of <0.001 was observed. Vitamin D showed a moderately negative corre lation (r= 0.347) with TSH with a p value of 0.008 in hypothyroid group. Conclusion: This study showed that though Vitamin D insufficiency was present in control group but this was progressed to deficiency in hypothyroid group. The decrease in serum Vitam in D levels was proportional to increase in serum TSH levels. Keywords: Hypothyroidism, Vitamin D, Serum TSH, 25(OH) D.
*Address for Correspondence: Dr. R. Priya, PG Student, Department of Biochemistry, M S Ramaiah Medical College, Bangalore 560054., Karnataka, INDIA. Email: [email protected] Received Date: 18/10/2015 Revised Date: 20/11/2015 Accepted Date: 14/12/2015
3. Tertiary Hypothyroidism Due to inadequate Access this article online secretion of TRH from hypothalamus. Quick Response Code: Primary hypothyroidism is most common among all Website: types. The aetiology of this could b e nutritional (Iodine www.medpulse.in deficiency), autoimmune (Hashimoto’s thyroiditis), iatrogenic (radio iodine ablation) and idiopathic. 3 Vitamin D is a fat soluble vitamin present in two forms DOI: 20 December cholecalciferol (vitamin D 3) and ergocalciferol (vitamin D2). Both forms ca n be found in foods or supplements, 2015 however vitamin D can be synthesized in skin from 7 3 dehydrocholesterol on exposure to Ultra Voilet B (UVB) rays. The provitamin produced is activated after INTRODUCTION hydroxlation at 25 and 1 alpha position by 25 Hypothyroidism is a common endocrine disorder that hydroxlasein liver and 1 alpha hydroxylase in kidney occurs due to the deficiency of thyroid hormone or its respectively. 4 effect on peripheral tissue. The prevalence of Serum 25(OH) D level is a better indicator of vitamin D 1 4 hypothyroidism in adults is around 10.95% in India. status than 1, 25(OH) 2 D because Hypothyroidism is classified as 2 1. 25(OH) D is the main circulating form of vitamin 1. Primary Hypothyroidism Due to insufficient D. production of thyroid hormone by thyroi d gland. 2. Serum 25(OH) D has longer half life as 2. Secondary Hypothyroidism Due to insufficient compared to 1,25 (OH) 2D. production of TSH from pituitary gland.
How to site this article: R Priya, K CVasudha, P Kalra . Serum vitamin D levels in primary hypothyroidism. MedPulse – International Medical Journal. December 2015; 2(12): 953 957. http://www.medpulse.in (accessed 22 December 2015). MedPulse – International Medical Journal, ISSN: 2348-2516, EISSN: 2348-1897, Volume 2, Issue 12, December 2015 pp 953-957
3. The technique to measure serum 25(OH) D is consent was taken from all participants in this study. simpler than the more complicated methods for Eighty six subjects were included in this study. They measuring serum 1, 25 (OH) 2 D. were classified into two main groups: Vitamin D belongs to the family of steroid hormones Group I “control group”: Itincluded 29 apparently having its own nuclear hormone receptor. 5 Classically the healthy individuals [Male (21.03%) and Female role of vitamin D is on calcium/phosphorus metabolism (78.95%)], their median ages with interquartile range and on skeletal system. Recent studies have seen its non were 31(26.5 35.5) years. They were not complaining of skeletal effects including immunomodulatory effect. The any chronic medical diseases, with normal clinical demonstration of vitamin D receptor in monocytes, examinations, there was no history of thyroid diseases or dendritic cells and activated T cells indicates significant any chronic illness which may interfere with results. They interaction between vitamin D and the immune system. 6 were not on Vitamin D supplements. Vitamin D insufficiency/deficiency has become a global Group II “Hypothyroid patients”: It included health problem. It has been seen in various studies that an 57patients [Male (20.69%) and Female (79.31%)], their inverse relationship exists between serum vitamin D median ages with interquartile range were 31(25.5 35.5) levels and autoimmune thyroiditis. Results of the study years. They were diagnosed as hypothyroid patients if done by Goswami R et al 7 indicated the presence of a serum TSH level was higher than 4.5 mU/L with normal 12 significant inverse association between 25 (OH) D levels or lower levels of serum total T 4. and TPOAb positive autoimmune thyroid disease. In the All participants included in this study were subjected to study done by Kivity et a l8 they showed that 79% of HT the followings: Complete history taking. Complete patients have 25(OH) D < 10ng/mL. Vitamin D has been clinical examination. Laboratory investigations, shown to influence thyrocytes directly by attenuating including: TSH stimulated iodide uptake and cell growth. 9 Vitamin Routine investigations D receptor (VDR) and Thyroid hormones receptors (TR) Serum T 3, T 4 and TSH, with reference range (1.3 ‑3.1 both are members of nuclear hormone receptor family nmol/Lfor T 3 ), (66 ‑181 nmol/L for T 4) and (l0.270 4.20 which includes receptor for glucocorticoids, IU/mL for TSH ). These analytes were estimated on mineralocorticoids, sex hormones, and vitamin A Cobas 6000 e601 automated analyzer by metabolites or retinoids. Both VDR and TR after binding Electrochemiluminenscense (ECLIA) method. with forms heterodimers with Retinoid X Receptor Research investigations (RXR). The complex then binds with specific Hormone Estimation of serum 25 (OH) D levels using Enzyme Responsive Element (HRE), VDRE (vitamin D linked immunosorbent assay (ELISA) kit method. The kit responsive element) and TRE (thyroid hormone response was from Calbiotech Inc. USA. This method was basedon element) respectively for vitamin D and thyroid hormone. the principle of competitive binding. A fixed amount of The association of ligand with these receptors results in biotin labeled vitamin D competes with the endogenous dissociation of co repressor. The liganded receptor is Vitamin D in the sample, standard, or quality control capable of binding one or more co activators with high serum for a fixed number of binding sites on the anti affinity. This results in recuirtment of RNA polymerase ΙΙ 10 Vitamin D antibody. Bound Vitamin D Biotin was and activation of gene transcription. As vitamin D and detected with Streptavidin HRP (SA HRP).Addition of thyroid hormone has similar mechanism of action at TMB Reagent and incubation at room temperature for 30 molecular level, there is a possibility of association of minutes, resulted the development of blue color. The vitamin D deficiency and hypothyroidism. This 11 color development was stopped with the addition of stop association is yet to be definitely proved.ChaiourkitL et solution, and the absorbance was measured al has seen in their population based health study that spectrophotometrically at 450 nmwavelength. Vitamin D higher 25 (OH) D levels were independently associated deficiency was defined as a serum level of 25(OH) D of ≤ with lower TSH in younger individuals. As Vitamin D 20 ng/ml and insufficiency as a serum levelbetween >20 affects thyroid hormone action in varied way, this study ng/ml and <30ng/ml and normal ≥ 30 ng/ml. 13 was done to see the relationship between primary hypothyroidism and serum Vitamin D levels. RESULTS Results were statistically analyzed by SPSS 20.0 for MATERIALS AND METHODS Windows. All the variables were presented as median It was a case control cross sectional study done at M S with interquartile range (25 th percentile 75 th percentile) Ramaiah Medical College and Hospitals, Bangalore for a due to non gaussian distribution of variables. The period of one year. Ethical clearance was obtained from Kolmogrov Smirnov method was used to test for College’s Ethical Committee for this study. Written normality of data distribution. Mann Whitney U test was
MedPulse – International Medical Journal, ISSN: 2348-2516, EISSN: 2348-1897, Volume 2, Issue 12, December 2015 Page 954 R Priya, K CVasudha, P Kalra
used to compare the results between the studied groups. Table 2: The correlation of different variables with Vitamin D in The associations between the variables in a group were different groups analyzed using Spearman test as correlation coefficient (r) Control group Hypothyroid group r = 0.09 r = 0.26 and their significance (p value). Results were considered Total T 3(nmol/L) significant when p value was <0.05. The median values p = 0.62 p = 0.05 r = 0.10 r = 0.27 with interquartile range of all studied parameters, in all Total T (nmol/L) 4 p = 0.60 p = 0.04 studied groups are shown in table1.There was no r = -0.03 r = -0.34 TSH(μIU/mL) statistical difference (P > 0.05) between groups regarding p = 0.87 p = 0.008 age. In control group no correlation was not significant Table 1: Table showing the demographic data and laboratory between Vitamin D and other parameters. The parameters of the study group hypothyroid group has shown a significant correlation. Control group (n=29) Hypothyroid group Median(Interquartile (n=57) Median p-value The thyroid hormones showed a weak positive correlation range) (Interquartile range) with Vitamin D, this correlation was statistically Age (yrs) 31(26.5-35.5) 31(25.5- 37.5) 0.76 significant (p value of 0.05 and 0.04 for T 3 and T 4 Total respectively). Serum TSH showed a negative correlation 1.79(1.54-1.92) 1.45(1.11-1.73 <0.001 * T3(nmol/L) with r value of 0.34 and a strong statistically significant p Total 105.2(96.31- 119.05) 87.66(57.07-101.36) <0.001 * value of 0.008. The scatter plots derived for showing T4(nmol/L) correlation of TSH with Vitamin D in hypothyroid group * TSH(μIU/mL) 2.27(1.69- 2.9) 11.9(6.63-75.68) <0.001 is shown in figure (1). Vitamin 26.2(20.45-32.8) 14.9(13.4-21.35) <0.001 * D(ng/mL)
Serum Vitamin D levels in control group was showing median value of 26.2 ng/mL with interquartile range of 20.45 32.8 ng/mL.Serum Vitamin D levels in hypothyroid group was showing median value of 14.9 ng/mL with interquartile range of 13.4 21.35 ng/mL The control group range was showing insufficiency or sufficiency but hypothyroid group has median value and range showing deficiency in cases. Using Mann Whitney U test for comparison between the two group, Vitamin D Figure 1: Correlations between serum TSH and Vit D Levels in showed a p value of <0.001. Similar results were found hypothyroid patients Gender distribution in different groups is shown in figure for serum T 3, T 4 and TSH. The intragroup spearman correlation coefficient derived between Vitamin D and (2) and (3) as percentage. other parameters is shown in table (2).
Figure 2 Figure 3 Legend Figure 2: Pie diagram showing gender distribution in control group Figure 3: Pie diagram showing gender distribution in hypothyroid group
Copyright © 2015, Statperson Publications, MedPulse – International Medical Journal, ISSN: 2348-2516, EISSN: 2348-1897, Volume 2, Issue 12 December 2015 MedPulse – International Medical Journal, ISSN: 2348-2516, EISSN: 2348-1897, Volume 2, Issue 12, December 2015 pp 953-957
DISCUSSION are the common causes of this condition. Both Vitamin D Vitamin D is known for its primary role inbone and hormone receptors and Thyroid hormone receptors mineral homeostasis, and it has been shown recently that belong to nuclear hormone receptor family and have the its deficiency is associated with various diseases such as same mechanism of action. Both the receptors are cardiovascular disease, cancer, infection, and adiposity as expressed on most of the tissues. The role of Vitamin D well as osteoporosis. Few studies have been conducted to in the mechanism of auto immune disease is being studied find any significant association between the levels of extensively and one of the roles postulated is in the Vitamin D and hypothyroidism and to determine whether pathogenesis of hypothyroidism. The current study was Vitamin D deficiency involves in the pathogenesis of undertaken to see the association of serum Vitamin D hypothyroidism or rather a consequence of the disease. levels with serum TSH in primary hypothyroidism. The These studied yielded conflicting results. The present hypothyroid cases were chosen based on the serum TSH study showed serum Vitamin D deficiency in hypothyroid levels as already mentioned. Serum thyroid hormones and group. The decrease in Vitamin D was proportional to serum TSH was assayed by ECLIA. Serum Vitamin D increase in serum TSH levels. This increase in TSH levels and serum TPO Ab was assayed by ELISA method. This with fall in Vitamin D observed in the present study was was a case control study involving eighty six subjects. in accordance with a study done by Zhang et al 14 on The statistical analysis was done using Mann Whitney U Chinese population where they found that high Vitamin D test. The correlations were presented as Spearman status was associated with low levels of TSH irrespective correlation coefficient. The results showed serum Vitamin of thyroid hormones status. On correlating Vitamin D D insufficiency/ deficiency in most of the study subjects. with TSH in hypothyroid group a significant correlation The decrease in Vitamin D levels was more evident in was seen. This finding from this study suggests a possible hypothyroid cases as compared to euthyroid controls. A association of hypovitaminosis D with hypothyroidism. good correlation between Vitamin D and TSH in This observation is consensus with a study done by hypothyroid cases was observed. 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Copyright © 2015, Statperson Publications, MedPulse – International Medical Journal, ISSN: 2348-2516, EISSN: 2348-1897, Volume 2, Issue 12 December 2015